Abstract:
BACKGROUND:Tubulointerstitial fibrosis is a morphologic hallmark of chronic kidney disease and is a key factor in the prediction of progression to end-stage renal failure. Disruption of tubular basement membrane and interstitial extracellular matrix (ECM) via cytokine-induced alterations in matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) may be an important mechanism in this process. The presence of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and their effects on proximal tubular cells may be critical in this process. METHODS:Human proximal tubular cells were cultured in hormonally defined medium. Cells at 80% confluency were exposed to TNF-alpha (0.1 to 100 ng/mL) or IL-1beta (0.1 to 100 ng/mL) or a combination of both for 48 hours. Activity and expression of MMP-9 was examined by gelatin zymography and Western blot analysis. TIMP-1 expression was analyzed by Western blotting. Signaling through cytokine receptors, protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways was investigated. RESULTS:TNF-alpha but not IL-1beta resulted in a dose-dependent increase in the latent form of MMP-9. TIMP-1 was decreased by treatment with either TNF-alpha or IL-1beta. Cotreatment with IL-1beta abolished the induction of MMP-9 but augmented the inhibition of TIMP-1 in the presence of TNF-alpha. Inhibition of PKC provided evidence of the importance of this pathway in mediating the cytokine-induced suppression of TIMP-1 in human kidney (HK-2) cells. Activation of the extracellular signal-regulated protein kinase (ERK1/2) MAPK mediated the up-regulation of MMP-9 by TNF-alpha whereas p38 was found to be involved in the IL-1beta-mediated inhibition of TNF-alpha-stimulated MMP-9. CONCLUSION:The differential effects of TNF-alpha and IL-1beta on proximal tubular MMP-9 and TIMP-1 expression are mediated through the TNF-RI, the IL-1-RI and the different signaling pathways of PKC, ERK1/2, and p38 MAPK. These findings may provide new insights into the role of proinflammatory cytokines TNF-alpha and IL-1beta in the development and possible therapeutic intervention in tubulointerstitial fibrosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Nee LE,McMorrow T,Campbell E,Slattery C,Ryan MPdoi
10.1111/j.1523-1755.2004.00900.xsubject
Has Abstractpub_date
2004-10-01 00:00:00pages
1376-86issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)50204-4journal_volume
66pub_type
杂志文章abstract:BACKGROUND:The impact of obesity on survival in end-stage renal disease (ESRD) patients as related to dialysis modality (i.e., a direct comparison of hemodialysis with peritoneal dialysis) has not been assessed adjusting for differences in medication use, follow-up > or =2 years, or accounting for changes in dialysis m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00385.x
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:The continuous chemical, physical, and inflammatory insults of prolonged continuous ambulatory peritoneal dialysis (CAPD) incite mesothelial cell responses, which may result in peritoneal fibrosis. The transforming growth factor-beta (TGF-beta), especially the isoform TGF-beta 1, has long been known to play ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00861.x
更新日期:2003-04-01 00:00:00
abstract::Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidne...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002519
更新日期:2007-11-01 00:00:00
abstract::Using a combination of intra-operative digital photography and micro-biopsy we measured renal cortical and papillary changes in five patients with primary hyperparathyroidism and abundant calcium phosphate kidney stones. Major tissue changes were variable papillary flattening and retraction, dilation of the ducts of B...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.161
更新日期:2008-07-01 00:00:00
abstract::Iron is critical for cellular, organismal, and possibly universal existence. Use of iron complexes to treat human diseases is ancient and is described in detail in Ayurveda/Siddha systems of medicine. Old aphorisms from Siddha medicine ("Alavukku Minjinal Amirdhamum Nanjagum," an elixir turns poisonous when taken in e...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.02.035
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:The T allele of the G protein beta3 subunit (GNB3) C825T polymorphism has been associated with increased signal transduction, increased activity of the kidney Na+/H+ exchanger, and also with late-onset essential hypertension. Hypertension is a strong independent risk factor for progression in IgA nephropathy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00734.x
更新日期:2004-07-01 00:00:00
abstract::Although it has been recognized for more than 140 years that the pacemaker driving pyeloureteric peristalsis resides within the kidney, the cellular mechanisms underlying this autorhythmicity have been little investigated. The demonstration by Hurtado et al. of a role of hyperpolarization-activated cation channels in ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.485
更新日期:2010-03-01 00:00:00
abstract::Cherney and co-workers examine the functional phenotype of the G894T eNOS polymorphism in a selected group of apparently healthy subjects. The investigators used L-arginine infusion and induced changes in renal hemodynamics. While L-arginine increased effective plasma flow and glomerular filtration rate in GG subjects...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2008.605
更新日期:2009-02-01 00:00:00
abstract::Orskov and colleagues demonstrate the impact of birth weight on the mean age of end-stage renal disease (ESRD) in a large Danish ADPKD cohort. Each kilogram of birth weight extended the mean age of ESRD onset by 1.7 years. Placental insufficiency, activation of the renin-angiotensin-aldosterone system, increased fetal...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.8
更新日期:2012-05-01 00:00:00
abstract::The effects of acidosis on renal function and morphology were examined in the isolated perfused rat kidney (IPK). Kidneys were perfused with oxygenated Krebs-Henseleit-albumin medium for 60 minutes at pH 7.4 or pH 7.0. At the lower pH, GFR was reduced by 25%, TRNa by 32% and oxygen consumption by 41% as compared to pe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.251
更新日期:1988-12-01 00:00:00
abstract:BACKGROUND:Cellular and molecular mechanisms responsible for cisplatin-induced nephrotoxicity to renal tubular epithelial cells are not well understood. Although caspases play a critical role in the execution of the cell death pathway, their specific role in toxic injury to renal tubular epithelial cells has not been e...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00026.x
更新日期:2001-11-01 00:00:00
abstract::The international guideline from Kidney Disease: Improving Global Outcomes suggests a hemoglobin target of 11 to 12 g/dl for children with chronic kidney disease. However, information to support this proposal is very limited in the pediatric population. Because of controversy, the unmet need is the establishment of an...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.10.006
更新日期:2017-01-01 00:00:00
abstract::Substantial evidence implicates impaired renal excretion of sodium as the major culprit in the pathogenesis of hypertension. The key question is: How does the impairment of Na+ excretion lead to increased peripheral vascular resistance and elevation of the blood pressure? Here we describe the evidence that elevated le...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.260
更新日期:1996-06-01 00:00:00
abstract::There is a paucity of studies describing malignancy-related mortality after kidney transplantation. To help quantify this, we extracted data for all kidney-alone transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed between Hospital Episode Statistics and the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.458
更新日期:2014-06-01 00:00:00
abstract::A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1995.161
更新日期:1995-04-01 00:00:00
abstract::We have recently presented evidence that endogenous nitric oxide (NO) and prostaglandins (PGs) modulate angiotensin II (Ang II) action in microperfused afferent arterioles (Af-Arts). Because flow may be a physiological stimulus of endothelial release of NO and PGs, we tested the hypothesis that flow through the lumen ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.55
更新日期:1996-02-01 00:00:00
abstract:BACKGROUND:The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P red...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059003855.x
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Estradiol suppresses the synthesis of type I collagen by murine mesangial cells. However, neither the alpha 1(I) nor the alpha 2(I) collagen gene contains an estrogen-response element. Because estradiol modulates the transcription of several genes that lack an estrogen-response element but contain a regulato...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00376.x
更新日期:1999-04-01 00:00:00
abstract::Diagnosis and treatment of atherosclerotic renal artery stenosis (ARAS) in the elderly is a never-ending challenge for every nephrologist. Kalra et al. report that adjusted hazard ratios for ARAS increased threefold from 1992 to 2004 in 16 million United States Renal Data System participants aged 66 years or older. Ho...
journal_title:Kidney international
pub_type: 信件
doi:10.1038/ki.2009.326
更新日期:2010-01-01 00:00:00
abstract::Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001966
更新日期:2006-12-01 00:00:00
abstract::Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-induc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.03.010
更新日期:2017-08-01 00:00:00
abstract::Suzuki et al. analyzed a mouse model of erythropoietin-deficient anemia to show that during iron overload renal interstitial fibroblasts accumulate iron, and this impairs the hypoxia-driven transcription of the erythropoietin gene. The authors show that excess iron decreases levels of hypoxia-inducible transcription f...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.07.027
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Hyperuricemia has been linked to cardiovascular and renal diseases, possibly through the generation of reactive oxygen species (ROS) and subsequent endothelial dysfunction. The enzymatic effect of xanthine oxidase is the production of ROS and uric acid. Studies have shown that inhibiting xanthine oxidase wit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00273.x
更新日期:2005-05-01 00:00:00
abstract::Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 wee...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.283
更新日期:1990-11-01 00:00:00
abstract:BACKGROUND:Fistula failure has been classified as early and late. Early failure refers to those cases in which the arteriovenous (AV) fistula never develops to the point that it can be used or fails within the first 3 months of usage. It has been common practice to abandon these early failures; however, aggressive eval...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00210.x
更新日期:2003-10-01 00:00:00
abstract::Chronic kidney disease (CKD) accelerates muscle protein degradation by stimulating the ubiquitin proteasome system through activation of the E3 ligases, Atrogin-1/MAFbx and MuRF-1. Forkhead transcription factors (FoxOs) can control the expression of these E3 ligases, but the contribution of individual FoxOs to muscle ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.84
更新日期:2012-08-01 00:00:00
abstract::Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.376
更新日期:1992-10-01 00:00:00
abstract::Although much emphasis has been placed on screening for albuminuria in type II diabetic patients, less attention has been focused on the role of glomerular filtration rate (GFR) in the assessment of risk. Herein, we examined the association between GFR and vascular complications in a consecutive cohort of 5174 type II...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000061
更新日期:2006-01-01 00:00:00
abstract::We compared growth rate, food conversion ratio and morphology of the growth zone in female Sprague-Dawley rats with subtotal nephrectomy or sham operation. Both groups were either given vehicle or 1.4 IU/day recombinant human growth hormone (GH) by s.c. osmotic minipump, or 2.5 IU twice daily intraperitoneally for 14 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.7
更新日期:1988-01-01 00:00:00
abstract::Activation of cAMP signaling pathway was shown to inhibit some pathobiologic processes in mesangial cells (MC). We investigated whether adrenomedullin (ADM), a potent agonist of adenylate cyclase, is synthesized in MC and whether it can, via cAMP, suppress the generation of reactive oxygen metabolites (ROM) and prolif...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.413
更新日期:1997-10-01 00:00:00